[Inhibitory effect of insulin-like growth factor binding protein-related protein 1 on retinal angiogenesis via ERK signaling pathway].

To explore the inhibitory effect of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1), a novel anti-angiogenic factor, on retinal angiogenesis and its underlying molecular mechanisms. Experimental study. C57BL/6J mice were classified into three groups: control group (24), oxygen-induced retinopathy (OIR) non-intervention group (24) and OIR intervention group (72). The OIR mouse model was established using improved Smith's methods ( 96). Twelve-day-old mice in the OIR intervention group were randomly assigned into three groups receiving intravitreal injection of recombinant mouse IGFBP-rP1 (50 μg/L, 100 μg/L and 200 μg/L, respectively). Five days later, the proliferative neovascular responses were estimated by quantifying the new vessel area relative to the total retinal area in flattening retinas stained by high molecular FITC-Dextran and counting the number of neovascular cell nuclei breaking through the internal limiting membrane (ILM) in cross-sections. Retinal phosphor-ERK1/2 (p-ERK1/2), ERK1/2 and vascular endothelial growth factor (VEGF) protein expression was assessed by Western blot. In the fluorescence angiograms, irregular neovascularization and fluorescence leakage were observed in the OIR model. In the OIR non-intervention group, the expression of p-ERK1/2 and VEGF was significantly up-regulated in comparison with the control group (100.068, 0.000. 6.526, 0.003). The area ratios of new retinal vessels and the number of neovascular cell nuclei in mice receiving intravitreal injection of recombinant mouse IGFBP-rP1 both decreased significantly (1920, 0.000. 852.387, 0.000), following the down-regulation of retinal p-ERK1/2 protein expression (859.587, 0.000) and VEGF protein expression (24.301, 0.000) in a dose-dependent manner (0.05). There was no significant difference in ERK1/2 protein expression (0.05). IGFBP-rP1 inhibits retinal angiogenesis by blocking ERK signaling pathway and down-regulating VEGF expression. This highlights the potential importance of IGFBP-rP1 serving as a target of gene therapy for retinal neovascularization. .